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Facts about Iodine and Autoimmune Thyroiditis - Beck Natural ...

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<strong>Facts</strong> <strong>about</strong> <strong>Iodine</strong> <strong>and</strong> <strong>Autoimmune</strong> <strong>Thyroiditis</strong><br />

by Guy E. Abraham, MD<br />

Since the 2006 publication by Tang, et al, 1 reporting a positive association between iodization of<br />

salt in China <strong>and</strong> autoimmune thyroiditis (AIT), I have received a lot of calls <strong>and</strong> e-mails<br />

questioning the use of iodine in patients with autoimmune thyroiditis. Iodophobes were elated<br />

with this publication, which vindicated their iodophobic viewpoint. However, a year later in<br />

2007, the same authors, using the same data 2 retracted their original statement <strong>and</strong> concluded<br />

that: “Chronic iodine excess does not apparently increase the risk of autoimmune thyroiditis.”<br />

I will present some facts <strong>about</strong> iodine <strong>and</strong> autoimmune thyroiditis.<br />

In 1912, pathologist H. Hashimoto published in a German medical journal, 3 his histological<br />

findings in four thyroid gl<strong>and</strong>s removed at surgery: numerous lymphoid follicles; extensive<br />

connective tissue formation; diffuse round cell infiltration; <strong>and</strong> significant changes of the acinar<br />

epithelium. He called this pathology of the thyroid “struma lymphomatosa”, but it became<br />

popular under the name “Hashimoto thyroiditis”. At the time of Hashimoto’s publication,<br />

autoimmune thyroiditis was not observed in the US population until the iodization of salt.<br />

Hashimoto’s thyroiditis is now classified as goitrous AIT because the gl<strong>and</strong> is enlarged, in<br />

distinction to atrophic AIT where atrophy <strong>and</strong> fibrosis are predominant. Both conditions are<br />

chronic, progressing over time to hypothyroidism in a significant percentage of patients. 4<br />

In several communities worldwide, an increased incidence of AIT was reported following<br />

implementation of iodization of sodium chloride. 5 In areas of the US where this relationship has<br />

been studied, mainly in the Great Lakes Region, a similar trend was reported. In 1966 <strong>and</strong> 1968,<br />

Weaver, et al, 6,7 from Ann Arbor, Michigan reported: “The salient histopathological feature of<br />

the thyroid gl<strong>and</strong>s, removed at operation in a five-year period before iodine prophylaxis (1915-<br />

1920), was the paucity of lymphocytes in their parenchyma <strong>and</strong>, more importantly, the absence<br />

of thyroiditis of any form … It should be emphasized that the thyroid gl<strong>and</strong>s prior to the use of<br />

iodized salt were devoid of lymphocytes, <strong>and</strong> nodular colloid goiters with dense lymphocytic<br />

infiltrates were found after the introduction of iodized salt in 1924.”


Furszyfer, et al, 8 from the Mayo Clinic, studied the average annual incidence of Hashimoto’s<br />

thyroiditis among women of Olmsted County, Minnesota, during three consecutive periods<br />

covering 33 years of observation, from 1935 to 1967. They found the incidence to be higher in<br />

women 40 years <strong>and</strong> older versus women 39 years <strong>and</strong> younger. However, in both groups, there<br />

was a progressive increase in the incidence of Hashimoto’s thyroiditis over time. During the<br />

three periods evaluated — 1935-1944; 1945-1954; 1955-1967 — the average annual incidence of<br />

Hashimoto’s per 100,000 population were 2.1, 17.9, <strong>and</strong> 54.1 for women 39 years <strong>and</strong> less. For<br />

women 40 years <strong>and</strong> older, the average annual incidence over the same three periods were 16.4,<br />

27.4, <strong>and</strong> 94.1.<br />

It is important to point out that the Mayo Clinic study started 10-15 years after implementation of<br />

iodization of salt in the area. Therefore, even during the first decade of observation, the<br />

prevalence of AIT was already significant. Again, it must be emphasized that prior to the<br />

implementation of iodized salt as observed by Weaver, et al, 6,7 this pathology of the thyroid<br />

gl<strong>and</strong> was not reported in the US, even though Lugol solution <strong>and</strong> potassium iodide were used<br />

extensively in medical practice at that time in daily amounts two orders of magnitude greater<br />

than the average intake of iodide from table salt. 4 This suggests that inadequate iodide intake<br />

aggravated by goitrogens, not excess iodide, was the cause of this condition. To be discussed<br />

later, AIT cannot be induced by inorganic iodide in laboratory animals unless combined with<br />

goitrogens, therefore inducing iodine deficiency.<br />

The pathophysiology of AIT is poorly understood. Experimentally induced autoimmune<br />

thyroiditis in laboratory animals by acutely administered iodide required the use of antithyroid<br />

drugs, essentially goitrogens, to produce these effects. 9-12 These goitrogens induced thyroid<br />

hyperplasia <strong>and</strong> iodide deficiency. Antioxidants either reduced or prevented the acute iodideinduced<br />

thyroiditis in chicks 13 <strong>and</strong> mice. 14 Bagchi, et al, 13 <strong>and</strong> Many, et al, 14 proposed that the<br />

thyroid injury induced by the combined use of iodide <strong>and</strong> goitrogens occurs through the<br />

generation of reactive oxygen species.<br />

We have previously proposed a mechanism for the oxidative damage caused by low levels of<br />

iodide combined. with antithyroid drugs: 2 Inadequate iodide supply to the thyroid gl<strong>and</strong>,<br />

aggravated by goitrogens, activates the thyroid peroxydase (TPO) system through elevated TSH,<br />

low levels of iodinated lipids, <strong>and</strong> high cytosolic free calcium, resulting in excess production of<br />

H 2 O 2 . The excess H 2 O 2 production is evidenced by the fact that antioxidants used in Bagchi’s<br />

experiments did not interfere with the oxidation <strong>and</strong> organification of iodide <strong>and</strong> therefore<br />

neutralized only the excess oxidant. 11 This H 2 O 2 production is above normal due to a deficient<br />

feedback system, caused by high cytosolic calcium due to magnesium deficiency <strong>and</strong> low levels<br />

of iodinated lipids which requires for their synthesis iodide levels two orders of magnitude<br />

greater than the RDA for iodine. 4 Once the low iodide supply is depleted, TPO in the presence of<br />

H 2 O 2 <strong>and</strong> organic substrate reverts to its peroxydase function, which is the primary function of


haloperoxydases, causing oxidative damage to molecules nearest to the site of action: TPO <strong>and</strong><br />

the substrate thyroglobulin (Tg). Oxidized TPO <strong>and</strong> Tg elicit an autoimmune reaction with<br />

production of antibodies against these altered proteins with subsequent damage to the apical<br />

membrane of the thyroid cells, resulting in the lymphocytic infiltration <strong>and</strong> in the clinical<br />

manifestations of Hashimoto’s thyroiditis. Eventually, the oxidative damage to the TPO results<br />

in deficient H 2 O 2 production. Hypothyroidism occurs in AIT when oxidation <strong>and</strong> organification<br />

of iodide in the thyroid gl<strong>and</strong> become deficient enough to affect synthesis of thyroid hormones.<br />

In vitro studies with purified fractions of calf thyroid gl<strong>and</strong>s by De Groot, et al, 15 gave<br />

compelling evidence that iodide at 10-5 molar confers protection to TPO against oxidative<br />

damage. To achieve peripheral levels of 10-5 molar iodide, a human adult needs a daily amount<br />

of 50-100 mg. DeGroot’s findings can be summarized as follows:<br />

• TPO is inactivated by H 2 O 2 .<br />

• KI at 10-5 molar protects TPO from oxidative damage.<br />

• Potassium bromide <strong>and</strong> potassium fluoride do not share this protective effect of KI.<br />

• The protective effect of KI is not due to the covalent binding of iodine to TPO but due to the<br />

presence of KI itself in the incubation media.<br />

The concentrations of iodine measured in the thyroid of patients with AIT are the lowest<br />

observed. Further, AIT patients with hypothyroidism have significantly lower iodine levels in the<br />

thyroid gl<strong>and</strong> than AIT patients with normal thyroid function. For the US population, Okerlund 16<br />

reported a mean value of around 10 mg iodine/ thyroid, with a range of 4-19 mg. In 56 patients<br />

suffering from autoimmune thyroiditis, but with normal thyroid function, a mean value of 4.8<br />

mg/thyroid was reported. In 13 patients with autoimmune thyroiditis <strong>and</strong> hypothyroidism, the<br />

mean value was 2.3 mg/thyroid.<br />

Based on the above facts, it is obvious that iodine deficiency, not excess, is the cause of AIT.<br />

REFERENCES


1) Teng, et al. “Effect of iodine intake on thyroid disease in China.” New Engl<strong>and</strong> Medical<br />

Journal, 2006; 354:2783-93.<br />

2) Yang F, et al. “Chronic iodine does not increase the incidence of hyperthyroidism: A<br />

prospective community-based epidemiological survey in China.” Eur J Endocrinol, 2007;<br />

156(4):403-8.<br />

3) Hashimoto H. “Zur Kenntniss der lymphomatosen Ver<strong>and</strong>erung der Schilddruse (Struma<br />

lymphomatosa).” Arch Klin Chir, 1912; 97:219-248.<br />

4) Abraham GE. “The safe <strong>and</strong> effective implementation of orthoiodosupplementation in medical<br />

practice.” The Original Internist, 2004; 11(1):17-36.<br />

5) Gaitan E, Nelson NC, <strong>and</strong> Poole GV. “Endemic goiter <strong>and</strong> endemic thyroid disorders.” World<br />

J Surg, 1991; 15:205-215.<br />

6) Weaver DK, Batsakis JG, <strong>and</strong> Nishiyama RH. “Relationship of iodine to ‘lymphocytic<br />

goiters.’” Arch Surg, 1968; 98:183-186.<br />

7) Weaver DK, Nishiyama RH, et al. “Surgical thyroid disease.” Arch Surg, 1966; 92:796-801.<br />

8) Furszyfer J, Kurl<strong>and</strong> LT, et al. “Hashimoto’s thyroiditis in Olmsted County, Minnesota, 1935<br />

through 1967.” Mayo Clin Proc, 1970; 45:586-596.<br />

9) Weetman AP. “Chronic autoimmune thyroiditis.” In: Werner & Ingbar’s The Thyroid.<br />

Braverman LE <strong>and</strong> Utiger RD, editors. Lippincott Williams & Wilkins, 2000; 721-732.<br />

10) Follis RH. “Further observations on thyroiditis <strong>and</strong> colloid accumulation in hyperplastic<br />

thyroid gl<strong>and</strong>s of hamsters receiving excess iodine.” Lab Invest, 1964; 13:1590-1599.<br />

11) Belshaw BE <strong>and</strong> <strong>Beck</strong>er DV. “Necrosis of follicular cells <strong>and</strong> discharge of thyroidal iodine<br />

induced by administering iodide to iodine-deficient dogs.” J Clin Endocr Metab, 1973; 13:466-<br />

474.<br />

12) Mahmoud I, Colin I, et al. “Direct toxic effect of iodine in excess on iodine-deficient thyroid<br />

gl<strong>and</strong>: epithelial necrosis <strong>and</strong> inflammation associated with lipofuscin accumulation.” Exp Mol<br />

Pathol, 1986; 44:259-271.<br />

13) Bagchi N, Brown TR, <strong>and</strong> Sundick RS. “Thyroid cell injury is an initial event in the<br />

induction of autoimmune thyroiditis by iodine in obese strain chickens.” Endocrinology, 1995;<br />

136:5054-5060.<br />

14) Many MC, Papadopoulaous J, et al. “<strong>Iodine</strong>-induced cell damage in mouse hyperplastic<br />

thyroid is associated to lipid peroxidation.” In: Progress in Thyroid Research. Gordon A, Gross J,<br />

<strong>and</strong> Hennenian G, editors. Proceedings of the 10th International Thyroid Conference. Balkema,<br />

Rotterdam, 1991; 635-638.<br />

15) DeGroot Leslie J, et al. “Studies on an iodinating enzyme from calf thyroid.” Endocrinology,<br />

1965; 76:632-645.<br />

16) Okerlund MD. “The clinical utility of fluorescent scanning of the thyroid.” In: Medical<br />

Applications of Fluorescent Excitation Analysis. Kaufman <strong>and</strong> Price, editors. CRC Press, Boca<br />

Raton, Florida, 1979; 149-160.

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